Loss of surface-bound antibody accompanying the anti-complementary modulation of leukemic B cell immunoglobulin: contrasting effects of antibodies directed against idiotypic and constant regions.
Guinea pig L2C leukemic lymphocytes display at their surfaces monoclonal IgM, which when compared with antibody undergoes rapid redistribution and variable endocytosis. One consequence of this is that the cells can prove resistant to lysis by complement subsequently added to the system, a process termed here anti-complementary modulation. We studied quantitatively the extent of antibody loss accompanying the modulation by radioimmunolabeling the cell surfaces with 125I-Fab' gamma fragments from an anti-antibody. Antibody directed against the constant region of the IgG light chain (anti-lambda) gave modulation effective against syngeneic (guinea pig strain 2) complement that closely paralleled the disappearance of anti-lambda from the cell surfaces. Antibody directed against the idiotypic region of the light chain (anti-Id) was as effective as anti-lambda in modulating against syngeneic complement. However, the bulk of the anti-Id was seen by radioimmunolabeling to persist on the surfaces of the resistant cells, even after prolonged exposure at 37 degrees C, and was shown by immunofluorescence to be in a patched configuration. In contrast to the results with syngeneic complement, modulation effective against rabbit complement appeared to have an absolute requirement for clearing of the antibody: thus anti-lambda could modulate, anti-Id could not. The differences observed between anti-lambda and anti-Id could not be accounted for by differences in their isotypic (Ig subclass) composition nor by the numbers of antibody molecules bound. Studies with directly fluoresceinated and 125I-labeled anti-lambda revealed endocytosis rather than shedding was the major route of antibody loss from the cell surfaces over the period of anti-complementary modulation. The findings are discussed in relation to mechanisms that enable leukemic B lymphocytes to escape destruction when confronted by antibody and complement.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004705:Endocytosis; D006168:Guinea Pigs; D007127:Immunoglobulin Constant Regions; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D007152:Immunologic Capping; D007942:Leukemia, Experimental / Q000276:immunology*; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*
D000888:Antibodies, Anti-Idiotypic; D007127:Immunoglobulin Constant Regions; D007130:Immunoglobulin Idiotypes; D007146:Immunoglobulin lambda-Chains; D011947:Receptors, Antigen, B-Cell; D003165:Complement System Proteins